Relapse and regression to severe wasting in children under 5 years: A theoretical framework.

Systematic reviews have highlighted that repeated severe wasting after receiving treatment is likely to be common, but standardised measurement is needed urgently. The Council of Research & Technical Advice for Acute Malnutrition (CORTASAM) released recommendations on standard measurement of relapse (wasting within 6 months after exiting treatment as per recommended discharge criteria), regression (wasting within 6 months after exiting treatment before reaching recommended discharge criteria) and reoccurrence (wasting after 6 months of exit from treatment as per recommended discharge criteria). We provide a theoretical framework of post-treatment relapse and regression to severe wasting to guide discussions, risk factor analyses, and development and evaluations of interventions. This framework highlights that there are factors that may impact risk of relapse and regression in addition to the impact of contextual factors associated with incidence and reoccurrence of severe wasting more generally. Factors hypothesised to be associated with relapse and regression relate specifically to the nutrition and health status of the child on admission to, during and exit from treatment and treatment interventions, platforms and approaches as well as type of exit from treatment (e.g., before reaching recommended criteria). These factors influence whether children reach full recovery, and poorer nutritional and immunological status at exit from treatment are more proximate determinants of risk of severe wasting after treatment, although post-treatment interventions may modify risks. The evidence base for many of these factors is weak. Our framework can guide research to improve our understanding of risks of relapse and regression and how to prevent them and inform programmes on what data to collect to evaluate relapse. Implementation research is needed to operationalise results in programmes and reduce post-treatment severe wasting at scale

Prognostic value of different anthropometric indices over different measurement intervals to predict mortality in 6-59-month-old children.

OBJECTIVE: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children. DESIGN: Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations. SETTING: Community-based, prospective studies from twelve countries in Africa and Asia. PARTICIPANTS: Children aged 6-59 months living in the study areas. RESULTS: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone. CONCLUSIONS: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions

Relapse after severe acute malnutrition: A systematic literature review and secondary data analysis.

The objectives of most treatment programs for severe acute malnutrition (SAM) in children focus on initial recovery only, leaving post-discharge outcomes, such as relapse, poorly understood and undefined. This study aimed to systematically review current literature and conduct secondary data analyses of studies that captured relapse rates, up to 18-month post-discharge, in children following recovery from SAM treatment. The literature search (including PubMed and Google Scholar) built upon two recent reviews to identify a variety of up-to-date published studies and grey literature. This search yielded 26 articles and programme reports that provided information on relapse. The proportion of children who relapsed after SAM treatment varied greatly from 0% to 37% across varying lengths of time following discharge. The lack of a standard definition of relapse limited comparability even among the few studies that have quantified post-discharge relapse. Inconsistent treatment protocols and poor adherence to protocols likely add to the wide range of relapse reported. Secondary analysis of a database from Malawi found no significant association between potential individual risk factors at admission and discharge, except being an orphan, which resulted in five times greater odds of relapse at 6 months post-discharge (95% CI [1.7, 12.4], P = 0.003). The development of a standard definition of relapse is needed for programme implementers and researchers. This will allow for assessment of programme quality regarding sustained recovery and better understanding of the contribution of relapse to local and global burden of SAM

Prognostic value of different anthropometric indices over different measurement intervals to predict mortality in 6-59-month-old children

Objective: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height z-score (WHZ) and weight-for-age z-score (WAZ) for predicting death over periods of one, three and six months follow-up in children. Design: Pooled analysis of 12 prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within one, three and six months were compared for three individual anthropometric indices and their combinations. Setting: Community-based, prospective studies from 12 countries in Africa and Asia Participants: Children aged 6-59 months living in the study areas Results: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with one month follow-up compared to six months by 49% (95% CI: 30-69%) for MUAC <115 mm (p<0.001), 48% (95%CI: 9.4-87%) for WHZ <-3 (p<0.01) and 28% (95%CI: 7.6-42%) for WAZ <-3 (p<0.005). This was accompanied by an increase in false-positives of only 3% or less. For all durations of follow-up, WAZ <-3 identified more children who died and were not identified by WHZ <-3 or by MUAC <115 mm, 120 mm or 125 mm but the use of WAZ <-3 led to an increased false-positive ratio up to 16.4% (95%CI: 12.0-20.9%) compared to 3.5% (0.4-6.5%) for MUAC <115 mm alone. Conclusions: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false-positives. Combining two indices increases sensitivity but also increases false-positives among children meeting case definitions.publishedVersionPeer reviewe

How do children with severe underweight and wasting respond to treatment? A pooled secondary data analysis to inform future intervention studies

Children with weight-for-age z-score (WAZ) <−3 have a high risk of death, yet this indicator is not widely used in nutrition treatment programming. This pooled secondary data analysis of children aged 6–59 months aimed to examine the prevalence, treatment outcomes, and growth trajectories of children with WAZ <−3 versus children with WAZ ≥−3 receiving outpatient treatment for wasting and/or nutritional oedema, to inform future protocols. Binary treatment outcomes between WAZ <−3 and WAZ ≥−3 admissions were compared using logistic regression. Recovery was defined as attaining mid-upper-arm circumference ≥12.5 cm and weight-for-height z-score ≥−2, without oedema, within a period of 17 weeks of admission. Data from 24,829 children from 9 countries drawn from 13 datasets were included. 55% of wasted children had WAZ <−3. Children admitted with WAZ <−3 compared to those with WAZ ≥−3 had lower recovery rates (28.3% vs. 48.7%), higher risk of death (1.8% vs. 0.7%), and higher risk of transfer to inpatient care (6.2% vs. 3.8%). Growth trajectories showed that children with WAZ <−3 had markedly lower anthropometry at the start and end of care, however, their patterns of anthropometric gains were very similar to those with WAZ ≥−3. If moderately wasted children with WAZ <−3 were treated in therapeutic programmes alongside severely wasted children, we estimate caseloads would increase by 32%. Our findings suggest that wasted children with WAZ <−3 are an especially vulnerable group and those with moderate wasting and WAZ <−3 likely require a higher intensity of nutritional support than is currently recommended. Longer or improved treatment may be necessary, and the timeline and definition of recovery likely need review.publishedVersionPeer reviewe

Anthropometric criteria for best identifying children at high risk of mortality : A pooled analysis of 12 cohorts

Objective: To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. Design: A multiple cohort individual data meta-analysis of mortality risk (within six months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences modelled. Setting: Community-based cohort studies in 12 low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. Participants: Children aged 6 to 59 months Results: Of the 12 anthropometric case definitions, four (weight-for-age Z-score (WAZ) <-2), (mid-upper-arm circumference (MUAC) <125 mm), (MUAC <115 mm or WAZ <-3), and (WAZ <-3) had the highest informedness in predicting mortality. A combined case definition (MUAC <115 mm or WAZ <-3) was better at predicting deaths associated with weight-for-height Z-score (WHZ) <-3 and concurrent wasting and stunting (WaSt) than the single WAZ <-3 case-definition. After assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC <115 mm or WAZ <-3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1.87 times larger than programmes admitting on MUAC <115 mm alone. Conclusions: A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.publishedVersionPeer reviewe

Anthropometric deficits and the associated risk of death by age and sex in children aged 6-59 months: A meta-analysis.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < -2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits

A Study of Steric Inhibition of the Pfitzinger Reaction

(From Introduction) A survey of the Pfitzinger reaction reveals that little attention has been given to the steric factors likely to govern the course of the condensation; a major part of the research done has dealt with its value as a synthetic tool. The primary purpose of this work was to add further information concerning steric inhibition in the Pfitzinger reaction; it was also hoped that the cinchoninic acids obtained might show physiological activity